LINDANE-INDUCED ELIMINATION OF GAP JUNCTIONAL COMMUNICATION IN RAT UTERINE MYOCYTES IS MEDIATED BY AN ARACHIDONIC ACID-SENSITIVE CAMP-INDEPENDENT MECHANISM

Previous studies by this laboratory showed that the pesticide lindane rapidly and potently inhibits gap junctional communication in myometri al smooth muscle cells. This study examined the possible role of cAMP or arachidonic acid in lindane's elimination of myometrial gap junctio nal communication. Lindane produced concentration-dependent increases in cAMP of 1.21, 2.94, 6.06, and 8.69 pmol/mg protein with 0.1, 1, 30, and 100 mu M lindane, respectively, compared to solvent-treated contr ols (1.27 pmol/mg protein). Lindane also increased release of tritiate d arachidonic acid to 342, 509, 852, 1236, 1639, and 4454 dpm/mu g pro tein with 0.01, 0.1, 1, 10, and 100 mu M lindane, respectively, compar ed to solvent controls (342 dpm/mu g protein). Transfer of Lucifer Yel low dye was used as a measure of gap junctional communication. Both 8- br-cAMP (98, 97, 54, and 4% transfer seen with 0, 1, 10, and 100 mu M cAMP) and arachidonic acid (98, 73, 54, 31, and 0% dye transfer for 0. 1, 1, 10, 100, and 1000 nM arachidonic acid) depressed dye transfer in cultured myocytes. Although the adenylate cyclase inhibitor 2',3'-did eoxyadenosine completely reversed forskolin-induced depression of dye transfer (1 mu M forskolin, 22% transfer), it had no effect with linda ne, indicating that lindane's depression of dye transfer was independe nt of adenylate cyclase activation. Lindane's inhibition of dye transf er was effectively reversed by growing myometrial cells under arachido nic acid-free conditions in the presence of eicosapentaenoic acid, a f atty acid that competes with arachidonic acid for the sn-1,2 position of membrane phospholipids: 0, 15, 40, and 88% dye transfer occurred in the presence of 0.01, 0.1, 1, and 10 mu M eicosapentaenoic acid with 30 mu M lindane. This implies that arachidonic acid release may be a c ritical event associated with lindane's inhibition of gap junctional c ommunication in uterine myocytes. (C) 1995 Academic Press, Inc.